Comparative Assessments of Screening Strategies for Melanoma Project Summary This grant proposal is centered around research problems arising in the early detection of malignant melanoma with an emphasis on sex-based differences in the early diagnosis of melanoma. The principal research areas include: (i) Investigate the natural history of melanoma and develop stochastic models for early detection of melanoma, (ii) Evaluate the mortality benefit of potential screening programs in the general and high-risk populations, (iii) Establish a pilot database of individuals at high-risk of developing melanoma and evaluate the factors associated with the risk of developing melanoma and of fatal melanoma. The incidence of malignant melanoma in the U.S. has been steadily rising over the last 30 years and there are no population-based guidelines to screen for this relatively common and lethal cancer. The natural history of melanoma is not well-understood although age, sex, and race are risk factors in the general population. Radically different incidence rates and stage at diagnosis patterns between men and women suggest the disease progression process may be sex-specific. Known risk factors for developing the disease include personal history of melanoma, presence of atypical nevi, increased nevus count, presence of large congenital nevi, history of non-melanoma skin cancer, actinic damage and family history of melanoma and disease susceptibility genes. The first main aim of this research is to develop a stochastic model to evaluate the melanoma progression process and the sojourn time distribution in the preclinical disease state. This model will utilize data from the U.S. Surveillace Epidemiology and End Results (SEER) and Eastern Cooperative Oncology Group (ECOG) melanoma studies. The second aim compares the effectiveness of various screening scenarios, using mortality reduction from screening as a measure of benefit. Screening programs defined by starting/stopping ages and screening intervals as well as risk-based schedules will be evaluated. The third aim establishes a database of subjects at high-risk of developing melanoma. This database will utilize de-identified data from patients followed by members of the ECOG/Southwest Oncology Group (SWOG) Melanoma Prevention Working Group (MPWG) and Pigmented Lesion Subcommittee (PLS). Multiple risk factors for developing melanoma will be evaluated. Associations between the risk factors for developing melanoma and for fatal melanoma will also be investigated. Overall, the proposed research provides a foundation that is crucial in order to develop practical guidelines for early detection programs in melanoma. Programs for the general population as well as among individuals at higher risk of developing melanoma will be investigated.